1284P - Clinical utility of liquid biopsy for non-small cell lung cancer patients with ALK fusion variants treated with brigatinib

Background

Liquid biopsies (LB) are a non-invasive source of tumor molecular information. Here, we evaluate the clinical utility of LB for the management of ALK-positive non-small cell lung cancer (NSCLC) patients using RNA from platelets and extracellular vesicles (EVs), and circulating tumor DNA (ctDNA).

Methods

Blood and tissue samples were collected from 30 ALK-positive, stage IIIB-IV NSCLC patients prior to initiating first-line brigatinib treatment. Nucleic acids from formalin-fixed-paraffin embedded (FFPE) tissue and plasma samples were analyzed by next-generation sequencing (NGS) using the Oncomine Focus Assay or the TruSight Oncology 500 ctDNA panel, respectively. EVs and platelets were isolated from plasma samples by differential centrifugation and RNA within these compartments was evaluated by QuantStudio 3D Digital PCR System and, when possible, by nCounter.

Results

The overall response rate was 93% (95%CI: 75.1, 98.4). Patients were followed for a median of 33.6 months. Median duration of response was 14.7 months. The median progression-free survival (PFS) was 33.8 months (6.2 – NR months) and median overall survival (OS) was not reached (NR). NGS analysis of FFPE samples enabled the detection of ALK fusion variants in all samples. Eleven patients harbored EML4-ALK variant 1 (v1), 5 carried v2, and 7 harbored the V3 and 7 had other variants or a combination of more than one variant. There were no significant differences in survival outcomes according to the type of variant. LB analysis revealed fusion detection rates of 33% using EVs, 17% in platelets, and 71% by ctDNA NGS profiling. Additionally, ctDNA provided information about tumor mutational burden (TMB) and ctDNA levels. Patients with blood TMB below 80 mutation/Mb exhibited significantly improved outcomes in terms of progression-free survival (PFS) (HR= 0.11; 95%CI: 0.02-0.76). Similarly, those with low baseline ctDNA levels (Maximum VAF ≤1%) demonstrated significantly superior PFS (HR= 0.11; 95%CI: 0.02-0.61) and overall survival (OS) (HR= 0.14; 95%CI: 0.03-0.82) compared to counterparts with higher ctDNA levels.

Conclusions

Detection rate by ctDNA profiling is higher compared with RNA-based approaches and it is of prognostic significance.

Clinical trial identification

NCT04223596.

Editorial acknowledgement

Legal entity responsible for the study

Fundacion GECP/Spanish Lung Cancer Group.

Funding

Takeda.

Disclosure

All authors have declared no conflicts of interest.